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Phosphorylation of the p190 RhoGAP N‐terminal domain by c‐Src results in a loss of GTP binding activity
Author(s) -
Roof Richard W.,
Dukes Bernard D.,
Chang Jin-Hong,
Parsons Sarah J.
Publication year - 2000
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(00)01439-3
Subject(s) - phosphorylation , gtp' , proto oncogene tyrosine protein kinase src , tyrosine phosphorylation , sh2 domain , biochemistry , tyrosine , microbiology and biotechnology , biology , sh3 domain , binding domain , chemistry , binding site , enzyme
p190 RhoGAP is a multi‐domain protein that is thought to regulate actin cytoskeleton dynamics. It can be phosphorylated both in vitro and in vivo at multiple sites by the Src tyrosine kinase and one or more of these sites is postulated to modulate p190 function. One of the regions which is multiply phosphorylated by Src in vitro is the N‐terminal GTP binding domain. Using a partially purified, bacterially expressed recombinant protein that includes the GTP binding domain (residues 1–389), we show that GTP binds to this fragment in a specific and saturable manner that is both time‐ and dose‐dependent and that tyrosine phosphorylation of this fragment by c‐Src results in a loss of GTP binding activity. These findings suggest that tyrosine phosphorylation of the p190 N‐terminal domain can alter its ability to bind GTP.